The purpose of this research study is to determine the safety and efficacy of administering two doses of lerapolturev in residual disease (within tumor margins) after surgery, followed later by repeated injections of lerapolturev in the subcutaneous area (under the skin) around the lymph nodes of the head and neck for adult patients diagnosed with recurrent glioblastoma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.
The study will be conducted in two stages: Approximately twelve patients with recurrent supratentorial glioblastoma will enroll in stage 1. Stage 1 is a safety lead-in which will assess the safety of lerapolturev when infused twice, 4 days apart, via Convection Enhanced Delivery (CED) in the residual disease of recurrent Glioblastoma (GBM) patients following maximal safe resection of the enhancing/necrotic portion of the disease recurrence. A tissue biopsy of the area infused will be recommended 5 weeks (± 1 week) after the 2nd lerapolturev infusion via CED, if imaging changes suggest tumor progression vs. immune effect on the MRI obtained 4-5 weeks after the 2nd lerapolturev infusion via CED. Stage 2 is a Phase 2 randomized clinical trial to compare the efficacy and safety of two treatment regimens for recurrent GBM patients who undergo maximal safe resection for their recurrence. Approximately eighty patients with recurrent supratentorial glioblastoma will enroll in stage 2 of the study. Stage 2 has 2 arms and is randomized, like the flip of a coin. Arm 1 is Lerapolturev and Arm 2 is Lomustine. After the recurrent tumor has been removed by surgery, subjects will be randomly assigned to receive either the FDA-approved chemotherapy (lomustine) or the study drug (lerapolturev). Subjects receive lerapolturev infused in the residual disease via CED twice, 4-day apart. About 1 week after the 2nd lerapolturev infusion, subjects will start subcutaneous (under the skin) injections of lerapolturev into the area of the cervical lymph nodes (head and neck) nearest to their tumor weekly for 4 weeks and afterward every 3 weeks for about a year. Subjects assigned to receive lomustine will begin taking it 3-4 weeks after surgery to remove their recurrent tumor. One prescribed dose of lomustine will be taken no more than once every 6 weeks, for no more than 1 year or up to 9 cycles. Subjects will be followed for serious adverse events (side effects) for 30 days after stopping the study. Subjects' medical records will be reviewed for the remainder of their life, in order to collect data on subsequent treatments, disease progression, tumor size/volume, and survival. There are risks to the study drug, lerapolturev, and the chemotherapy drug, lomustine. The most common risks of lerapolturev are headache, seizure, weakness on one side of the body, difficulty thinking or processing, difficulty receiving or responding to sensory information, fatigue, and difficulty speaking or comprehending. Risks associated with infusion procedure include mild discomfort at the infusion site, bleeding in the brain, pain, infection, and swelling of the brain. The study drug and procedures used together could also potentially cause more serious side effects. The most common risks of lomustine are changes in your red blood cell count, changes in platelets, changes in your liver, feeling confused and tired, poor appetite, and loss of ability to conceive or father a child.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
92
Lerapolturev (intratumoral) will be dosed at 2x108 TCID50 in 3.0 mL x 2 doses (total dose 4x108 TCID50) by Convection Enhanced Delivery. For the patients randomized to the lerapolturev Arm 1 of Stage 2, seven days (±2 days) following completion of the 2nd intratumoral infusion of lerapolturev, patients will begin cervical perilymphatic subcutaneous injection of lerapolturev at a dose of 2 x 108 TCID50 (in 0.5 ml diluent) around the cervical lymph node chain ipsilateral to the intracranial tumor.
Lomustine will be given as a single oral dose of 110 mg/m2 every six weeks for up to 9 cycles.
Duke University Medical Center
Durham, North Carolina, United States
RECRUITINGProportion of patients at each dose level who experienced a dose-limiting toxicity - Stage 1
Dose-limiting toxicities (DLTs) are defined as any of the following events that are possibly, probably, or definitely attributable to study treatment (i.e., lerapolturev) during dose escalation (Stage 1): * Any Grade 3 or any Grade 4 toxicity within 2 weeks, including cerebral edema or worsening neurologic symptoms * Any life-threatening event within 2 weeks * Treatment-related death at least possibly, probably, or definitely attributable to study treatment * Any grade 2 or higher serious cytokine release syndrome at least possibly, probably, or definitely attributable to study treatment, particularly those affecting vital organs (e.g., cardiac, hepatic, renal, CNS) occurring within 2 weeks of the infusion
Time frame: Up to 1 year
Proportion of patients who experience an unacceptable toxicity - Stage 2
Unacceptable toxicity is defined as any of the following events that are possibly, probably, or definitely attributable to study treatment: * Any Grade 3 or any Grade 4 toxicity within 2 weeks, including cerebral edema or worsening neurologic symptoms * Any life-threatening event within 2 weeks * Treatment-related death at least possibly, probably, or definitely attributable to study treatment * Any grade 2 or higher serious cytokine release syndrome at least possibly, probably, or definitely attributable to study treatment, particularly those affecting vital organs (e.g., cardiac, hepatic, renal, CNS) occurring within 2 weeks of the infusion
Time frame: Up to 1 year
Overall survival (OS) - Stage 2
Median OS, where OS is defined as the time between randomization and death
Time frame: 2 years
Progression free survival (PFS)
Median PFS, where PFS is defined as the time between randomization and initial failure (disease progression or death)
Time frame: 2 years
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